What does IgG (Immunoglobulin G) positivity in dengue indicate?

IgG Positivity in Dengue: Interpretation and Clinical Significance

IgG positivity in dengue indicates a past dengue infection or a current secondary infection, which has important implications for disease severity and clinical management. 1

Interpretation of Dengue IgG Results

• Positive IgG with negative IgM typically indicates past dengue infection (not a current infection) 1
• Positive IgG with positive IgM suggests a current secondary dengue infection (reinfection with a different serotype) 1
• When IgG is positive without confirmatory plaque reduction neutralization test (PRNT), it should be interpreted as "presumptive recent flavivirus infection" 1
• IgG antibodies can persist for months to years after infection, making them useful markers of previous exposure 1

Primary vs. Secondary Dengue Infection

• Primary dengue infection is characterized by positive IgM with negative IgG (IgM+ plus IgG-) 2
• Secondary dengue infection is characterized by positive IgG with either positive or negative IgM (IgG+ plus IgM+/-) 2
• Secondary infections account for approximately 62% of dengue cases in endemic regions 2

Clinical Significance of IgG Positivity

• Secondary dengue infections (indicated by IgG positivity) are associated with higher risk of severe disease forms including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) 3, 4
• The mechanism for increased severity in secondary infections involves antibody-dependent enhancement (ADE), where pre-existing non-neutralizing IgG antibodies facilitate viral entry into cells 4
• IgG antibodies with enhanced affinity for the activating Fc receptor FcγRIIIA (due to afucosylated Fc glycans) are associated with thrombocytopenia and increased disease severity 4

Diagnostic Algorithm for Dengue

1. For patients with symptoms ≤7 days:

   • Perform dengue NS1 antigen test and/or NAAT (nucleic acid amplification test) 1, 5
   • Also perform IgM and IgG antibody testing 1

2. For patients with symptoms >7 days:

   • Perform IgM and IgG antibody testing 1
   • Consider PRNT for confirmation if available 1

3. Interpretation of combined results:

   • Positive NS1/NAAT with negative IgM/IgG: Acute primary dengue infection 1, 5
   • Positive NS1/NAAT with positive IgG: Acute secondary dengue infection 1, 6
   • Negative NS1/NAAT with positive IgM and negative IgG: Recent primary dengue infection 1, 2
   • Negative NS1/NAAT with positive IgM and positive IgG: Recent secondary dengue infection 1, 2
   • Negative NS1/NAAT with negative IgM and positive IgG: Past dengue infection 1

Common Pitfalls in Interpretation

• Cross-reactivity with other flaviviruses (like Zika virus) can complicate interpretation of IgG results 1
• Without confirmatory PRNT, positive IgG results should be interpreted cautiously as "presumptive" 1
• A positive IgG test alone cannot determine the timing of infection 1
• IgG tests have limited utility for diagnosis in the acute phase (first 4-5 days) of primary infection 5, 7
• Combined testing approaches (NS1/IgM/IgG) provide higher diagnostic accuracy than single tests 7

Clinical Management Implications

• Patients with positive IgG (indicating secondary infection) should be monitored more closely for warning signs of severe disease 6, 4
• Laboratory confirmation of secondary infection (positive IgG) should prompt consideration of more intensive supportive care and monitoring 3, 4
• In endemic areas, IgG positivity rates can help estimate the attack rate and population immunity levels 2